Treatment patterns and adherence to lipid-lowering drugs during eight-year follow-up after a coronary heart disease event.

BACKGROUND AND AIMS: Proper prescription and high adherence to intensive lipid lowering drugs (LLD) in patients with coronary heart disease (CHD) are crucial and strongly recommended. The aim of this study is to investigate long-term treatment patterns and adherence to LLD following hospitalization for a CHD event. METHODS: Patients admitted to two Norwegian hospitals with a CHD event from 2011 to 2014 (N = 1094) attended clinical examination and completed a questionnaire, median 16 months later. Clinical data were linked to pharmacy dispensing data from 2010 to 2020. The proportions using high-intensity statin therapy (atorvastatin 40/80 mg or rosuvastatin 20/40 mg) and non-statin LLD after the CHD event were assessed. Adherence was evaluated by proportion of days covered (PDC) and gaps in treatment. RESULTS: Median age at hospitalization was 63 (IQR 12) years, 21 % were female. Altogether, 1054 patients (96 %) were discharged with a statin prescription, while treatment was dispensed in 85 % within the following 90 days. During median 8 (SD 2.5) years follow-up, the proportion using high-intensity statin therapy ranged 62-68 %, whereas the use of ezetimibe increased from 4 to 26 %. PDC <0.8 was found in 22 % of statin users and 26 % of ezetimibe users. The proportions with a treatment gap exceeding 180 days were 22 % for statins and 28 % for ezetimibe. Smoking at hospitalization and negative affectivity were significantly associated with reduced statin adherence, regardless of adherence measure. CONCLUSIONS: In this long-term follow-up of patients with CHD, less than 70 % used high-intensity statin therapy with only small changes over time, and only 25 % used additional treatment with ezetimibe. We identified factors associated with reduced statin adherence that may be target for interventions.

A multi-component intervention increased access to smoking cessation treatment after hospitalization for atherosclerotic cardiovascular disease: a randomized trial.

Aims: To evaluate the effects of a multi-component intervention for smokers hospitalized for atherosclerotic cardiovascular disease (ASCVD) on the participation rate in community-based cessation programmes and the use of cessation drugs. Additionally, to explore the impact on the cessation rates at 6 months. Methods and results: A randomized parallel-group study was conducted at a Norwegian secondary care hospital in 2021. The intervention group was: (i) counselled using motivational interviewing techniques during hospitalization; (ii) given an information leaflet, detailing the cessation programme; and (iii) referred to the community-based smoking cessation treatment including a post-discharge pro-active telephone invitation. The control group received usual care and the same information leaflet containing clear contact details for initiating participation. Data were collected at baseline, 1, 3, and 6 months. Among 99 smokers hospitalized with ASCVD, 40 were excluded. Of 59 randomized patients, 4 were lost to follow-up and 55 completed the study. The mean age was 65.1 (standard deviation 9.3) years, 35% were female, and 88% had smoked >20 years. Co-morbidity was prevalent (mean Charlson score 4.8). The intervention group was more likely to participate in the smoking cessation treatment {48 vs. 7%, difference: 41% [95% confidence interval (CI): 14%, 63%]} and used cessation drugs more frequently [59 vs. 21%, difference: 38% (95% CI: 17%, 59%)]. At the 6 months point prevalence, we observed notable between-group differences in self-reported cessation rate (48 vs. 25%). Conclusion: The intervention significantly increased the participation rate at community-based smoking cessation programmes and the use of cessation drugs among multi-morbid smokers hospitalized for ASCVD.

Validation of a novel direct method to determine reduced adherence to atorvastatin therapy.

AIMS: Objective methods to determine statin adherence are requested to improve lipid management. We have recently established a method to detect reduced adherence to atorvastatin therapy with cut-off values based on the sum of atorvastatin and its major metabolites in blood. We aimed to validate this method in patients with and without cardiovascular disease, and optimize previous cut-off values. METHODS AND RESULTS: The pharmacokinetic study included 60 participants treated with atorvastatin 20 mg (N=20), 40 mg (N=20), and 80 mg (N=20). Atorvastatin was then stopped and blood samples collected from day zero to day four. Quantification of the parent drug and its metabolites in blood plasma was performed with a liquid chromatography-tandem mass spectrometry assay. The cut-off values for reduced adherence were validated and optimized by calculating diagnostic sensitivity and specificity. Our candidate cut-off value of dose-normalized six-component sum of atorvastatin plus metabolites <0.10 nM/mg provided a sensitivity of 97% and a specificity of 93% for detecting ≥2 omitted doses. An optimized cut-off <0.062 nM/mg provided a sensitivity of 90% and a specificity of 100%. An alternative simplified two-component metabolite sum with cut-off value <0.05 nM/mg provided a sensitivity of 98% and a specificity of 76%. An optimized cut-off <0.02 nM/mg provided a sensitivity of 97% and a specificity of 98%. CONCLUSION: This validation study confirms that our direct method discriminates reduced adherence from adherence to atorvastatin therapy with high diagnostic accuracy. The method may improve lipid management in clinical practice and serve as a useful tool in future studies.

Frailty, health literacy and self-care in patients admitted with acute heart failure. / Skrøpelighet, helsekompetanse og egenomsorg hos pasienter som innlegges med akutt hjertesvikt.

BACKGROUND: There is limited knowledge from Norway on clinical characteristics, self-care and health literacy in patients admitted to hospital with acute heart failure. Our aim was to identify these factors in this group. MATERIAL AND METHOD: We included patients admitted with acute heart failure over a period of six months (2022/2023) at Drammen Hospital and Vestfold Hospital Trust. Cardiac nurses collected information from the patients, including self-assessed knowledge on an ordinal scale from 0 (little knowledge) to 10 (good knowledge). Clinical frailty scores were calculated and data from the hospital records were recorded. RESULTS: Of 136 patients with acute heart failure, 81 were included. Median age was 79 (range 35-95) years, 35 (43 %) were women. A total of 35 (43 %) had been admitted with heart failure exacerbation in the past year. The patients had a median of 5 (1-10) diagnoses, and the median score on the clinical frailty scale was 4 (1-7), corresponding to 'vulnerable'. A total of 63 (78 %) had been diagnosed with heart failure before admission to hospital. Of these, 13 (21 %) were unaware of the diagnosis, and their self-assessed knowledge was median 3 (25th and 75th percentile, 0-5) for management of heart failure, 2 (25th and 75th percentile, 0-5) for lifestyle interventions and 0 (25th and 75th percentile, 0-2) for heart medications. Altogether 42 out of 63 (67 %) weighed themselves weekly, 13 (21 %) measured their blood pressure, while 3 (5 %) had a self-care plan. Of 50 patients with left ventricle ejection fraction ≤ 40 %, 32 (64 %) were discharged with betablockers and angiotensin II receptor blockers or a combination drug with a neprilysin inhibitor, whereas 11 (22 %) were also prescribed SGLT2 inhibitors and mineralocorticoid receptor antagonists. INTERPRETATION: The included patients were multimorbid and had a low level of self-care and health literacy. There is potential to optimise well-documented medicinal treatment.

Predictors of health-related quality of life in outpatients with coronary heart disease.

Introduction: Health-related quality of life (HRQoL) is an important treatment target in patients with coronary heart disease (CHD) and is associated with poor outcomes. Therefore, it is of clinical importance to identify the key determinants of HRQoL among these patients. There is, however, limited knowledge of how a comprehensive set of psychosocial factors influence HRQoL. We aimed to determine the relative associations of clinical and psychosocial factors with mental and physical components of HRQoL in a sample of CHD outpatients. Methods: This cross-sectional study included 1,042 patients 2-36 (mean 16) months after a CHD event recruited from two general Norwegian hospitals with a combined catchment area making up 7% of the Norwegian population, representative with regards to demographic and clinical factors. We collected data on HRQoL, demographics, comorbidities, coronary risk factors, and psychosocial factors. HRQoL was assessed using the Short Form 12 (SF12), which comprises a Mental Component Scale (MCS), and the Physical Component Scale (PCS). Crude and multi-adjusted linear regression analyses were used to investigate the association between covariates and MCS and PCS. Results: Mean age was 61 [standard deviation (SD) 10] years, 20% were females, 18% had type D personality, 20% significant depression symptoms, 14% significant symptoms of anxiety whereas 45% reported insomnia. The presence of type D personality (ß: -0.19), significant symptoms of depression (ß: -0.15), and the presence of insomnia (ß: -0.13) were negatively associated with MCS, but not PCS in multi-adjusted analyses. The presence of chronic kidney disease (ß: -0.11) was associated with reduced MCS, whereas the presence of chronic obstructive pulmonary disease (ß: -0.08) and low physical activity (ß: -0.14) were negatively associated with PCS. Younger age was associated with lower MCS, whereas older age was associated with lower PCS. Discussion: We conclude that Type D personality, depressive symptoms, insomnia, and chronic kidney disease were the strongest determinants of the mental component of HRQoL. Assessing and managing these psychological factors among CHD outpatients may improve their mental HRQoL.

Risk of recurrent cardiovascular events in coronary artery disease patients with Type D personality.

Introduction: Data on the association between Type D personality, its traits negative affectivity (NA) and social inhibition (SI), and risk of major adverse cardiac events (MACE) in coronary outpatients is sparse. Furthermore, the associations between Type D subgroups and cardiovascular risk factors are largely unknown. Methods: We investigated i) Type D personality, NA and SI and risk of recurrent MACE, and ii) the relationship between Type D subgroups and risk factors in a coronary population. This prospective cohort study included 1083 patients` median 16 months after a myocardial infarction and/or a revascularization procedure who were followed-up for 4.2 (SD 0.4) years. Type D personality was assessed by DS14. Anxiety and depression, statin adherence, and risk factors were assessed by patients' self-report and a clinical examination with blood samples. MACE, defined as cardiovascular death, myocardial infarction, revascularization, stroke or heart failure, were obtained from hospital records from index event to end of study lasting 5.7 years. Data were analyzed by Cox proportional hazard regression. Results: In all, 352 MACE occurred in 230 patients after average 4.2 years follow-up. Higher NA score was associated with MACE after adjustment for age, risk factors and comorbidity (HR 1.02 per unit increase, 95% CI 1.00-1.05), whereas we found a weaker, not statistically significant estimated effect of higher SI score. After additional adjustment for symptoms of anxiety and depression, we found a weaker, not statistically significant association between NA and MACE (HR 1.01 per unit increase, 95% CI 0.98-1.05). Low statin adherence and smoking were more prevalent in the Type D and high NA group. Discussion: Our results indicate that the NA trait is related to worse prognosis in outpatients with coronary artery disease.

Psychiatric disorders, rumination, and metacognitions in patients with type D personality and coronary heart disease.

BACKGROUND: Little is known regarding the prevalence of psychiatric disorders in patients with both coronary heart disease (CHD) and type D personality, and whether these patients may benefit from psychotherapy that modifies metacognitive beliefs implicated in disorder maintenance. This study explored prevalence rates among these patients and associations between type D characteristics, rumination and metacognitions. METHODS: Forty-seven consecutive patients with CHD who scored positive for type D personality were included in this pre-planned study. Participants underwent structured clinical interviews for mental and personality disorders and completed questionnaires assessing rumination and metacognitions. RESULTS: Mean age was 53.8 (SD 8.1) years and 21.3% were female. At least one mood disorder or anxiety disorder was found in 70.2% and 61.7% of the patients. The most common disorders were major depressive disorder (59.6%), social phobia (40.4%), and generalized anxiety disorder (29.8%). At least one personality disorder was detected in 42.6%. Only 21% reported ongoing treatment with psychotropic medication whereas none had psychotherapy. Metacognitions and rumination were significantly associated with negative affectivity (0.53-0.72, p < .001) but not social inhibition. CONCLUSION: Mood and anxiety disorders were highly prevalent and relatively untreated among these patients. Future studies should test the metacognitive model for type D personality.

Atorvastatin Metabolite Pattern in Skeletal Muscle and Blood from Patients with Coronary Heart Disease and Statin-Associated Muscle Symptoms.

Self-perceived statin-associated muscle symptoms (SAMS) are prevalent, but only a minority is drug-dependent. Diagnostic biomarkers are not yet identified. The local statin exposure in skeletal muscle tissue may correlate to the adverse effects. We aimed to determine whether atorvastatin metabolites in blood reflect the corresponding metabolite levels in skeletal muscle, and whether genetic variants of statin transporters modulate this relationship. We also addressed atorvastatin metabolites as potential objective biomarkers of SAMS. Muscle symptoms were examined in patients with coronary disease and self-perceived SAMS during 7 weeks of double-blinded treatment with atorvastatin 40 mg/day and placebo in randomized order. A subset of 12 patients individually identified with more muscle symptoms on atorvastatin than placebo (confirmed SAMS) and 15 patients with no difference in muscle symptom intensity (non-SAMS) attended the present follow-up study. All received 7 weeks of treatment with atorvastatin 40 mg/day followed by 8 weeks without statins. Biopsies from the quadriceps muscle and blood plasma were collected after each treatment period. Strong correlations (rho > 0.7) between muscle and blood plasma concentrations were found for most atorvastatin metabolites. The impact of the SLCO1B1 c.521T>C (rs4149056) gene variant on atorvastatin's systemic pharmacokinetics was translated into muscle tissue. The SLCO2B1 c.395G>A (rs12422149) variant did not modulate the accumulation of atorvastatin metabolites in muscle tissue. Atorvastatin pharmacokinetics in patients with confirmed SAMS were not different from patients with non-SAMS. In conclusion, atorvastatin metabolite levels in skeletal muscle and plasma are strongly correlated, implying that plasma measurements are suitable proxies of atorvastatin exposure in muscle tissue. The relationship between atorvastatin metabolites in plasma and SAMS deserves further investigation.

Statins seldom cause adverse reactions. / Statiner gir sjelden bivirkninger.

Statins seldom cause muscle side effects and are tolerated by the great majority of people. It is important to spend time, build trust, manage negative expectations and identify other causes of muscle problems than the use of statins.

Worry and rumination predict insomnia in patients with coronary heart disease: a cross-sectional study with long-term follow-up.

STUDY OBJECTIVES: Insomnia is highly prevalent and associated with anxiety and depression in patients with coronary heart disease patients. The development of effective psychological interventions is needed. Worry and rumination are potential risk factors for the maintenance of insomnia, anxiety, and depression that may be modified by psychological treatment grounded in the Self-Regulatory Executive Function model. However, the relationships between worry, rumination, anxiety and depression, and insomnia are not known. Therefore, we investigated these relationships both cross-sectionally and longitudinally among patients with coronary heart disease. METHODS: A cross-sectional study consecutively included 1,082 patients in 2014-2015, and 686 were followed up after mean of 4.7 years. Data were gathered from hospital records and self-report questionnaires comprising assessment of worry (Penn State Worry Questionnaire), rumination (Ruminative Responses Scale), anxiety and depression (Hospital Anxiety and Depression Scale), and insomnia (Bergen Insomnia Scale). RESULTS: Insomnia correlated moderately with all other psychological variables (R 0.18-0.50, all P values < .001). After adjustments for anxiety and depression, odds ratios for insomnia at baseline were 1.27 (95% confidence interval 1.08-1.50) and 1.60 (95% confidence interval 1.31-1.94) per 10 points increase of worry and rumination, respectively. Corresponding odds ratios for insomnia at follow-up were 1.28 (95% confidence interval 1.05-1.55) and 1.38 (95% confidence interval 1.09-1.75). Depression was no longer significantly associated with insomnia after adjustments for worry and rumination, but anxiety remained significant. CONCLUSIONS: Worry and rumination predicted insomnia both cross-sectionally and prospectively, even after controlling for anxiety and depression, although anxiety remained significant. Future studies may test psychological interventions targeting these factors in patients with coronary heart disease and insomnia. CITATION: Frøjd LA, Papageorgiou C, Munkhaugen J, et al. Worry and rumination predict insomnia in patients with coronary heart disease: a cross-sectional study with long-term follow-up. J Clin Sleep Med. 2022;18(3):779-787.

Insomnia as a predictor of recurrent cardiovascular events in patients with coronary heart disease.

Study Objectives: Insomnia is highly prevalent in patients with coronary heart disease (CHD). However, the potential effect of insomnia on the risk of recurrent major adverse cardiovascular events (MACE) remains uncertain. Methods: This prospective cohort study included 1082 consecutive patients 2-36 (mean 16) months after myocardial infarction and/or coronary revascularization. Data on clinical insomnia, coronary risk factors, and comorbidity were collected at baseline. Clinical insomnia was assessed using the Bergen Insomnia Scale (BIS). The primary composite endpoint of MACE (cardiovascular death, hospitalization due to myocardial infarction, revascularization, stroke, or heart failure) was assessed with an average follow-up of 4.2 (SD 0.3) years after baseline. Data were analyzed using Cox proportional hazard regression models stratified by prior coronary events before the index event. Results: At baseline, mean age was 62 years, 21% were females, and 45% reported clinical insomnia. A total of 346 MACE occurred in 225 patients during the follow-up period. For clinical insomnia, the relative risk of recurrent MACE was 1.62 (95% confidence interval [CI]: 1.24-2.11, p < .001) adjusted for age, gender, and previous coronary events. In a multi-adjusted analysis, including coronary risk factors, cardiovascular comorbidity, symptoms of anxiety, and depression, the relative risk was 1.41 (95% CI: 1.05-1.89, p = .023). Clinical insomnia accounted for 16% of the MACE in attributable risk fraction analyses, being third in importance after smoking (27%) and low physical activity (21%). Conclusions: Clinical insomnia was associated with increased risk of recurrent MACE. These results emphasize the importance of identifying and managing insomnia in CHD outpatients.

Clinical and psychological factors in coronary heart disease patients with statin associated muscle side-effects.

BACKGROUND: To compare clinical and psychological factors among patients with self-perceived statin-associated muscle symptoms (SAMS), confirmed SAMS, and refuted SAMS in coronary heart disease patients (CHD). METHODS: Data were obtained from a cross-sectional study of 1100 CHD outpatients and a study of 71 CHD outpatients attending a randomized, double-blinded, placebo-controlled, crossover study to test effects of atorvastatin 40 mg/day on muscle symptom intensity. Clinical and psychosocial factors were compared between patients with and without SAMS in the cross-sectional study, and between patients with confirmed SAMS and refuted SAMS in the randomized study. RESULTS: Bilateral, symmetric muscle symptoms in the lower extremities during statin treatment were more prevalent in patients with confirmed SAMS compared to patients with refuted SAMS (75% vs. 41%, p = 0.01) in the randomized study. No significant differences in psychological factors (anxiety, depression, worry, insomnia, type D personality characteristics) were detected between patients with and without self-perceived SAMS in the cross-sectional study, or between patients with confirmed SAMS and refuted SAMS, in the randomized study. CONCLUSIONS: Patients with confirmed SAMS more often present with bilateral lower muscle symptoms compared to those with refuted SAMS. Psychological factors were not associated with self-perceived SAMS or confirmed SAMS. A careful pain history and a search for alternative causes of muscle symptoms are likely to promote communication in patients with SAMS, and may reduce the risk for statin discontinuation.

Post-myocardial infarction rehabilitation and secondary prevention in hospitals. / Rehabilitering og sekundærforebygging etter hjerteinfarkt ved sykehus.

BACKGROUND: Norwegian studies have documented poor cardiovascular risk factor control and a high incidence of new cardiovascular events in myocardial infarction patients. There is little knowledge about the scope of secondary prevention treatment and cardiac rehabilitation in Norwegian hospitals. Therefore, we wanted to conduct a survey of discharge routines and outpatient follow-up after myocardial infarction. MATERIAL AND METHOD: In October 2018, the heads of cardiology departments and nurse managers/physiotherapists at cardiology outpatient clinics at all Norwegian hospitals (N = 51) were contacted and asked to take part in a telephone interview. RESULTS: A total of 40 doctors (78 %) and 51 nurses/physiotherapists (100 %) conducted the telephone interview. Eleven hospitals used standardised discharge summary templates with treatment targets and expected follow-up. Ten hospitals offered routine outpatient follow-up. A total of 47 hospitals (92 %) offered multidisciplinary cardiac rehabilitation, 'heart school' classes or cardiac exercise training, and of these 9 (18 %) offered multidisciplinary comprehensive cardiac rehabilitation in line with international recommendations. INTERPRETATION: The survey revealed considerable differences in reported discharge routines and the provision of cardiac rehabilitation and outpatient follow-up at Norwegian hospitals.

The relationship between directly measured statin adherence, self-reported adherence measures and cholesterol levels in patients with coronary heart disease.

BACKGROUND AND AIMS: We aimed to determine the relationship between statin adherence measured directly, and by self-report measures and serum cholesterol levels. METHODS: Patients prescribed atorvastatin (N = 373) participated in a cross-sectional study 2-36 months after a coronary event. Self-reported adherence included statin adherence the past week, the 8-item Morisky medication adherence scale (MMAS-8), and the Gehi et al. adherence question. Atorvastatin was measured directly in spot blood plasma by a novel liquid chromatography tandem mass-spectrometry method discriminating adherence (0-1 doses omitted) and reduced adherence (≥2 doses omitted). Participants were unaware of the atorvastatin analyses at study participation. RESULTS: Mean age was 63 (SD 9) years and 8% had reduced atorvastatin adherence according to the direct method. In patients classified with reduced adherence by the direct method, 40% reported reduced statin adherence, 32% reported reduced adherence with the MMAS-8 and 22% with the Gehi question. In those adherent by the direct method, 96% also reported high statin adherence, 95% reported high adherence on the MMAS-8 whereas 94% reported high adherence on the Gehi question. Cohen's kappa agreement score with the direct method was 0.4 for self-reported statin adherence, 0.3 for the Gehi question and 0.2 for the MMAS-8. Adherence determined by the direct method, self-reported statin adherence last week, and the Gehi question was inversely related to LDL-cholesterol levels with a p-value of <0.001, 0.001 and 0.004, respectively. CONCLUSIONS: Plasma-statin measurements reveal reduced adherence with higher sensitivity than self-report measures, relate to cholesterol levels, and may prove to be a useful tool to improve lipid management.

Insomnia in patients with coronary heart disease: prevalence and correlates.

STUDY OBJECTIVES: The aim of this study was to determine the prevalence of insomnia and its association with clinical and psychosocial factors in a large sample of outpatients with coronary heart disease. METHODS: The sample comprised 1,082 patients, mean age 62 years (21% female), who participated in the cross-sectional NORwegian CORonary Prevention Study. Patients who were hospitalized with myocardial infarction and/or a coronary revascularization procedure in 2011-2014 responded to a self-report questionnaire and participated in a clinical examination with blood samples 2-36 (mean, 16) months later. Insomnia was assessed using the Bergen Insomnia Scale, a questionnaire based on the criteria for the clinical diagnosis of insomnia as described in the Diagnostic and Statistical Manual of Mental Disorders, fourth version. We performed bivariate logistic regressions for crude analysis and backward stepwise logistic regressions for multiadjusted odds ratios (OR). RESULTS: In total, 488 patients (45%) reported insomnia, and 24% of these patients had used sleep medication in the previous week. Anxiety symptoms (OR: 5.61) were the strongest determinants of insomnia, followed by female sex (OR: 1.88), diabetes (OR: 1.83), eating fish fewer than three times a week (OR: 1.69), type D personality (OR: 1.69), and C-reactive protein ≥ 2 mg/L (OR:1.58), in multiadjusted analyses. CONCLUSIONS: Insomnia was highly prevalent in coronary heart disease outpatients. Psychological factors, lifestyle factors, and subclinical inflammation were associated with insomnia. Our results emphasize the need to identify patients with insomnia and provide appropriate management of insomnia in outpatients with coronary heart disease.

Effect of atorvastatin on muscle symptoms in coronary heart disease patients with self-perceived statin muscle side effects: a randomized, double-blinded crossover trial.

AIMS: To estimate the effect of atorvastatin on muscle symptom intensity in coronary heart disease (CHD) patients with self-perceived statin-associated muscle symptoms (SAMS) and to determine the relationship to blood levels of atorvastatin and/or metabolites. METHODS AND RESULTS: A randomized multi-centre trial consecutively identified 982 patients with previous or ongoing atorvastatin treatment after a CHD event. Of these, 97 (9.9%) reported SAMS and 77 were randomized to 7-week double-blinded treatment with atorvastatin 40 mg/day and placebo in a crossover design. The primary outcome was the individual mean difference in muscle symptom intensity between the treatment periods, measured by visual-analogue scale (VAS) scores. Atorvastatin did not affect the intensity of muscle symptoms among 71 patients who completed the trial. Mean VAS difference (statin-placebo) was 0.31 (95% CI: -0.24 to 0.86). The proportion with more muscle symptoms during placebo than atorvastatin was 17% (n = 12), 55% (n = 39) had the same muscle symptom intensity during both treatment periods whereas 28% (n = 20) had more symptoms during atorvastatin than placebo (confirmed SAMS). There were no differences in clinical or pharmacogenetic characteristics between these groups. The levels of atorvastatin and/or metabolites did not correlate to muscle symptom intensity among patients with confirmed SAMS (Spearman's rho ≤0.40, for all variables). CONCLUSION: Re-challenge with high-intensity atorvastatin did not affect the intensity of muscle symptoms in CHD patients with self-perceived SAMS during previous atorvastatin therapy. There was no relationship between muscle symptoms and the systemic exposure to atorvastatin and/or its metabolites. The findings encourage an informed discussion to elucidate other causes of muscle complaints and continued statin use.